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28 Cards in this Set
- Front
- Back
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NF tangles are composed of what?
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Insoluble tau protein in paired helical filaments.
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Where in the brain are NF tangles found?
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Hippocampus, entorhinal cortex, amygdala. Relative sparing of primary motor and sensory cortex.
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Neuropil threads
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Small tau-positive processes filled with paired helical filaments.
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Abnormality of tau
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Usually found in axons (binds and stabilizes microtubules); in NF tangles, it's abnormally phosphorylated
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Neuritic plaque
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Abnormal neurites surrounding a core of abnormal beta amyloid protein.
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Diffuse plaques
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Made of beta amyloid but lack the abnormal cell processes of neuritic plaques.
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Amyloid angiopathy
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Beta-amyloid found in blood vessel walls in cortex and meninges
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APP is found on which chromosome?
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Ch21
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The beta-amyloid portion is derived from which part of the APP?
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The hydrophobic transmembrane portion
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BAG secretases
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Beta secretase cleaves at the N terminus. Alpha secretase cleaves in the middle and releases harmless molecules. Gamma secretase cleaves at the carboxy terminus and is linked to presenilin 1 as well as Notch.
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APP mutations (familial AD) account for what percentage of AD?
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<0.1%
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Which secretase tends to form oligomers?
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Beta
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What is the harm of soluble oligomers?
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May do damage long before they are deposted in plaques. Inhibit long-term potentiation and may be responsible for early memory loss in AD.
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ApoE is produced by what?
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Astrocytes, microglia and liver cells
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Which apoE allele is associated with an increased risk of AD?
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ApoE4 (homozygotes have 5-8 times increased risk; heterozygotes have 2-3 times increased risk.
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What does apoE4 specifically influence?
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Age of onset of AD (not duration or severity of illness)
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AD vaccines have shown what?
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Decreased cortical plaques and beta-amyloid load, but no reduction in NF tangles or amyloid angiopathy.
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Second most common form of dementia
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Dementia with Lewy bodies
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To have LBD, the patient must have one of which symptoms?
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fluctuation in cognitive decline; visual hallucinations; extrapyramidal features
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Alpha-synuclein labels what?
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Lewy bodies
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Alpha-synuclein mutations are found in what?
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Familial Parkinson's Disease
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What changes occur in LBD?
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Spongy change in the temporal cortex
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Chromosome 17-linked FT dementia
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Mutation in gene encoding progranulin, or mutation in tau gene causing hyperorality, OCD, disturbances in cognitive function, Parkinsonisn
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Chromosome 3-linked FT dementia
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Mutations disrupt endosomal pathway.
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Chromosome 9-linked FT dementia
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Mutation in VCP, an ATPase. Associated with Paget's disease of the bone
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Pick's disease: where?
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FT atrophy with relative sparing of the posterior 2/3 of the superior temporal gyrus
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Pick bodies
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silver positive (argyrophilic), tau positive inclusions found within cytoplasm of neurons
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Pick cells
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Neurons with swollen, eosinophilic cytoplasm filled with neurofilaments
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